Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates. We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC.
He et al BMC Cancer 2014, 14:235 http://www.biomedcentral.com/1471-2407/14/235 RESEARCH ARTICLE Open Access Outcome after intensity modulated radiotherapy for anaplastic thyroid carcinoma Xiayun He1, Duanshu Li2, Chaosu Hu1, Zhuoying Wang2, Hongmei Ying1 and Yi Wu2* Abstract Background: Anaplastic thyroid carcinoma (ATC) is a malignancy with one of the highest fatality rates We reviewed our recent clinical experience with intensity modulated radiotherapy (IMRT) combined with surgery and chemotherapy for the management of ATC Methods: 13 patients with ATC who were treated by IMRT in our institution between October 2008 and February 2011, have been analyzed The target volume for IMRT was planned to include Gross tumor volume (GTV): primary tumor plus any N + disease (66 Gy/33 F/6.6 W), with elective irradiation of thyroid bed, bilateral level II through VI and mediastinal lymph nodes to the level of the carina (54-60 Gy) Seven patients received surgical intervention and eleven patients had chemotherapy Results: The median radiotherapy dose to GTV was 60 Gy/30 fractions/6 weeks The median survival time of the 13 patients was months The direct causes of death were distant metastases (75%) and progression of the locoregional disease (25%) Ten patients were spared dyspnea and tracheostomy because their primary neck lesion did not progress Conclusion: The results showed that IMRT combined by surgery and chemotherapy for ATC might be beneficial to improve locoregional control Further new therapies are needed to control metastases Keywords: Anaplastic thyroid carcinoma, ATC, Intensity modulated radiotherapy, Locoregional control, Distant metastases Background Anaplastic thyroid carcinoma (ATC) is a rare malignant tumor and accounts for 40 Gy versus ≤ 40 Gy, was 5.4 and 1.7 months, respectively (P < 0.001) [12] Another study indicated that median survival of patients receiving 40 Gy or more (n = 24) was longer than those with less than 40 Gy (n = 34) (9 vs months) [13] Compared with 2D, IMRT provides a more conformal high dose with improved homogeneity to the gross disease and high-risk areas, while lowering the dose to normal organs at risk, including spinal cord, epiglottis false/true vocal cords, pharyngeal constrictors and esophagus Our results compared to other report supported the hypothesis that IMRT may improve ATC outcome, especially local control Foote RL et al reported that ten patients (40%) had regionally confined ATC (stag IVA in patients, IVB in patients) were treated by IMRT combined with individualized surgery (where feasible), and chemotherapy The target volume included any residual cancer within the thyroid bed and/ regional lymph nodes, with elective treatment of bilateral level II- VI, mediastinal lymph nodes to the level of the carina, and received 57.6-70 Gy Five patients (50%) are alive and disease-free, and overall survival at and years was 70% and 60%, respectively [14] Our preliminary results of IMRT showed: the tolerance of patients was significantly improved, almost all patients received higher dose of radiation (> 54 Gy) Only two patients received 40 Gy and 54 Gy respectively and they gave up the radiotherapy because of esophagitis, but after one month their dysphagia improved Another patient with lung metastasis received 50 Gy and stopped concurrent radiochemotherapy (cisplatin) Instead he was given combined chemotherapy, the bigger neck mass became smaller and dyspnea was relieved Higher dose brought neck mass under control, 76.9% (10/13) patients obtained locoregional control (including complete and partial response and stable disease), thus avoiding tracheostomy due to breathing difficulties, which significantly improved the patient’s quality of life and survival The present study of IMRT in ATC showed an apparent improvement in median survival of 4-8 months, although the number of patients in this series is modest For patients with ATC, the main causes of death were failure of local control and distant metastases Multivariate analysis demonstrated that age ≥ 70 years, white blood cell (WBC) ≥ 10,000 mm3, extra-thyroidal invasion, distant metastases, avoidance of multimodality therapy, and radiation therapy with a dose of < 40 Gy were risk factors for poorer survival [6,15], but the most direct cause of death is upper airway obstruction as reported by Tashima L et al [5] In his study of 33 patients, dyspnea was the only independent factor affecting the survival For ATC, the opportunity of complete surgery is rare because of its extensive invasion and distant metastases Tracheotomy Page of procedures have to be performed to resolve dyspnea caused by compression by the neoplastic mass or bilateral laryngeal nerve palsy, but it was not shown to significantly increase survival time and may sacrifice quality of life [5] In this series of patients treated with IMRT, direct causes of death were distant metastases (6/8 patients) and locoregional progression (2/8 patients) Most of the patients present at diagnosis with metastatic disease, but almost all patients developed new metastasis during the rapid course of the disease Chemotherapy has been studied for many years, but it is still unclear as to which systemic therapy is the best Over the past few years, the most used agent in ATC is doxorubicin, cisplatin, 5-fluorouracil, and mitoxantrone, but the results of these drugs were disappointing In recent years, new drugs including paclitaxel, gemcitabine have been used to try to increase overall survival in patients with ATC, but until now they not seem to improve the outcomes significantly [16-20] In ATC patients reported at stage IVB (n = 9), IVC (n = 4), induction chemotherapy by weekly paclitaxel is a promising therapeutic strategy and responders can be expected to achieve long-term survival, compared to that of ATC patients at stage IVB treated without paclitaxel (n = 50) However, no significant difference of overall survival was observed in patients at stage IVC patients with or without weekly induction paclitaxel (n = 13) [18] In our series, cisplatin was combined with 5-fluorouracil, paclitaxel, and gemcitabine respectively, but there was no clear correlation between the specific chemotherapy administered and its outcome The main toxicity of radiotherapy was dysphagia and esophagitis, which may have made patients quit the radiotheraphy Five patients with ATC have been treated at the Tom Baker Cancer Centre, radiation therapy (RT) was delivered in two phase using a three-dimensional (3D) conformal technique, 60% of patients needed tube feeding and 20% required tracheostomy because of dysphagia or dyspnea [21] Troch M et al reported that a total of six patients with ATC received standard external beam RT of 60 Gy in 30 fractions alone with docetaxel, all patients developed severe esophagitis, which resulted in inability to swallow food and and thereafter needed parenteral nutrition Only three patients received the planned 60 Gy, other three patients discontinued at 40, 44, and 50 Gy because of side effects [22] As opposed to these results, the side effect in our study of IMRT was mild: none of the patients required tube feeding support or tracheostomy during radiotherapy There are limitations with our analyses: the dataset is relatively small considering the number of variables that were evaluated, thus limiting the impact of our analyses Conclusions In summary, our consecutive series of stage IVB, and IVC ATC patients treated with IMRT combined multimodality He et al BMC Cancer 2014, 14:235 http://www.biomedcentral.com/1471-2407/14/235 treatment demonstrates encouraging long-term survival with acceptable toxicity The main direct cause of death for ATC patients was distant metastases instead of airway obstruction New therapies need further investigation Competing interests The authors declare that they have no competing interests Authors’ contributions XH: Study design, data collection, data analysis, manuscript preparation, manuscript review DL: Study design, data collection, data analysis, manuscript preparation, manuscript review CH: Study design, manuscript preparation and review ZW: Study design and data collection HY: Study design and statistical analysis YW: Reviewed the draft, provided comments or revisions, and approved the final manuscript All authors read and approved the final manuscript Acknowledgements We acknowledge the fund by Fudan University Shanghai Cancer Center and support by Department of Radiation Oncology and Department of Head and Neck Surgery The views expressed in this publication are those of the authors Author details Department of Radiation Oncology, Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China 2Department of Head and Neck Surgery, Department of Oncology, Fudan University Shanghai Cancer Center, Shanghai Medical College, Fudan University, Shanghai 200032, China Received: 29 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